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Infection and Immunity, November 1998, p. 5443-5449, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Immunogenicity and Protective Efficacy of the WI-1 Adhesin of Blastomyces dermatitidis

Marcel Wüthrich, Wun-ling Chang, and Bruce S. Klein*

Departments of Pediatrics, Internal Medicine, and Medical Microbiology and Immunology and the Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792

Received 2 April 1998/Returned for modification 21 April 1998/Accepted 24 August 1998

People infected with Blastomyces dermatitidis develop strong immunity to the yeast surface adhesin WI-1, including antibody responses to the adhesive domain, a 25-amino-acid repeat, and cellular responses to the N terminus. We studied the immunogenicity of WI-1 and the ability of anti-WI-1 immune responses to protect against lethal pulmonary infection in mice. WI-1 immunization, given in Freund's adjuvant subcutaneously in two doses 2 weeks apart, evoked delayed hypersensitivity responses in a concentration-dependent manner. Immunized mice also had anti-WI-1 antibody responses, with titers reaching an endpoint dilution of approximately 1:800,000. Anti-WI-1 immunoglobulin G (IgG) antibody subclasses were IgG1 > IgG2b > IgG2a > IgG3, indicating a mixed T helper 1 and T helper 2 immune response. In protection experiments, WI-1 immunization significantly prolonged the survival of C57BL/6 and BALB/c mice compared to controls following intranasal administration of a lethal dose of B. dermatitidis yeasts (Kaplan-Meier survival curve P values of 0.027 to 0.0002) and also protected a proportion of the animals from death due to progressive pulmonary blastomycosis. Taken together, our results suggest that administration of WI-1 raises antibody and cell-mediated immune responses, which enhance resistance against pulmonary infection with B. dermatitidis. Mechanisms of vaccine-induced resistance require further investigation.

* Corresponding author. Mailing address: University of Wisconsin Hospitals and Clinics, 600 Highland Ave., K4/434, Madison, WI 53792. Phone: (608) 263-9217. Fax: (608) 263-0440. E-mail: BRKlein{at}vms2.macc.wisc.edu.

Infection and Immunity, November 1998, p. 5443-5449, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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